Abstract 6345: How surgical site infection influences breast cancer cell recurrence and cancer cell reprogramming
Authors: Ruth Í. O'Connor, Amira F. Mahdi, Joanne Nolan, Catríona M. Dowling, Colum P. Dunne, Patrick A. Kiely
Journal: Cancer Research (2022)

Abstract Breast cancer is the most prevalent form of cancer worldwide, with surgery remaining a standard treatment. Although a treatable disease, with the survival rate improving due to enhancements in screening and treatment, cancer recurrence remains a dominant contributor to breast cancer related deaths. It has been suggested that systemic factors during the postoperative period, such as surgical site infection (SSI), may increase the risk of recurrence, although the exact role that these infections play in breast cancer recurrence has yet to be elucidated. To investigate the influence of these SSIs in breast cancer recurrence following primary breast cancer surgery, we conducted a systematic literature review1 to examine both the incidence and risk factors related to SSI after primary breast cancer surgery and the contribution of SSIs to breast cancer recurrence. Data were extracted from 99 studies for the SSI-focused searches, and 53 studies for recurrence-focused searches and we found that there was a 13.07% mean incidence of SSIs. 638 Gram-positive and 442 Gram-negative isolates were identified, with Staphylococcus aureus and Escherichia coli appearing as the most abundant bacteria in SSIs of breast cancer patients. 11.8% cases of cancer recurrence were noted, however confounding factors of retrospective study design, surgery type and SSI definition make results challenging to compare and interpret. Only five studies investigated the association between SSI and breast cancer recurrence, three of which highlighting a positive correlation between SSI and breast cancer recurrence. To further explore this link, we are using in vitro models to investigate the molecular mechanisms by which both Gram-positive and Gram-negative bacteria affect the phenotype of breast cancer. Using LTA (a component of the cell wall of Staphylococcus aureus) to model Gram-positive bacteria and LPS (a component of the Escherichia coli cell wall) to model Gram-negative bacteria, we examined the effects of LTA and LPS on the behavior of MCF-7, MDA-MB-231 and ZR-75-1 cells. Using qRT-PCR, we found that treatment of cells with LPS and LTA dysregulates the expression of pro-tumorigenic inflammatory markers TNF-a and IL-6 in MDA-MB-231 cells. Separately, using metabolomic profiling on LPS and LTA treated MDA-MB-231 cells, we observe significant metabolic reprogramming of the cells when stimulated with the bacterial mimics. We believe that these findings may lead to a better understanding of how SSI promotes breast cancer recurrence and may help design surgical procedures and target therapies. 1O’Connor, R. Í., Kiely, P. A., &amp; Dunne, C. P. (2020). The relationship between post-surgery infection and breast cancer recurrence. A systematic review. Journal of Hospital Infection. 106, (522-535) https://doi.org/10.1016/j.jhin.2020.08.004. Citation Format: Ruth Í. O'Connor, Amira F. Mahdi, Joanne Nolan, Catríona M. Dowling, Colum P. Dunne, Patrick A. Kiely. How surgical site infection influences breast cancer cell recurrence and cancer cell reprogramming [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6345.